Clinical Trial Uses Immune System Booster to Fight Sepsis

Researchers say the use of Interleukin-7 is a departure from traditional treatments that have relied on antibiotics and inflammatory medications that tamp down the immune system.

A small clinical trial shows that a drug used to rev up the immune system could effectively treat sepsis.

Researchers at Washington University School of Medicine in St. Louis said their findings are a potential breakthrough in the fight against sepsis, which claims about 250,000 lives each year.

The use of immune system boosting drugs is a marked departure from standard treatments for sepsis that involve high doses of antibiotics that fight the infection, but which fail to boost the body’s immune defenses.

The results were published Thursday in JCI Insight.

The trial involved 27 sepsis patients, ages 33 to 82, who were treated at Barnes-Jewish Hospital in St. Louis, Vanderbilt University Medical Center in Nashville or two medical centers in France — Dupuytren University Hospital in Limoges and Edouard Herriot Hospital in Lyon.

The study authors concede that the trial was too small to see a statistical benefit in mortality. However, senior investigator Richard S. Hotchkiss, MD, said there was an improved immune response in patients who were given a drug to beef up their immunity.

"Mortality rates from sepsis have remained essentially the same over the last 50 years. Hundreds of drugs have been tried and have failed," said Hotchkiss, a professor of anesthesiology, of medicine and of surgery.

"It may sound counterintuitive when inflammation is such a problem early in sepsis, but our approach is to stimulate certain immune cells to help the patient's system take control of the infection," he said.

The patients were treated with a drug made of interleukin-7 (IL-7).

"IL-7 reverses the marked loss of CD4 and CD8 T cells, a hallmark of sepsis and a likely key pathophysiological event responsible for the morbidity and mortality of the disorder," Hotchkiss said.

Co-investigator Edward R. Sherwood, MD, a professor of anesthesiology at Vanderbilt, said patients suffering from septic shock often have low counts of these key immune cells.

"We believe that could play a role in the development and course of sepsis because without those cells, patients aren't able to clear as much harmful bacteria," Sherwood said.

The patients in the trial were hospitalized with septic shock and were randomly assigned to one of two therapies. Seventeen patients received the IL-7 drug, and 10 received a standard treatment. Those who received the drug experienced a threefold to fourfold increase in CD4 and CD8 counts.

"Even though the study was small, we were encouraged that IL-7 helped restore key cells in the immune systems of these patients," said Andrew H. Walton, a staff scientist in the Hotchkiss lab and co-author of the study. "Overall, that should help improve patient survival."

The research showed that IL-7 boosts the ability of CD4 and CD8 T cells help recruit other immune cells to kill bacteria that cause infections.

"IL-7 represents a potential new way forward in the treatment of sepsis by targeting the patient's immune system," Hotchkiss said. "This has a major advantaged caused by targeting the host, and should be effective against many diverse pathogens.”

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Traditional approaches to sepsis therapy do not address patients' severely compromised immune systems. Without restoring immune function, Hotchkiss said, many patients develop lingering infections and are helpless to fight any new infections.

"We know that 40% of patients die in the 30- to 90-day period after the initial septic infection," Hotchkiss said. "Their bodies can't fight secondary infections, such as the blood infections and staph infections that can develop later on because their immune systems are shot. By strengthening adaptive immunity with IL-7 and increasing the numbers of CD4 and CD8 cells available to help fight infections, we think this approach can make a big difference."

As a next step, a larger trial is planned involving 300 to 400 patients, which Hotchkiss should have the statistical strength to determine whether IL-7 can improve survival rates.